A prospective multicenter study for comparison of standard-dose repeated bolus injection vs. low-dose continuous intravenous infusion of terlipressin for acute esophageal variceal bleeding in patients with liver cirrhosis

초록

Background and aims: Acute esophageal variceal bleeding (AVB) is one of the most serious complications of liver cirrhosis. For the emergent management of variceal bleeding, administration of a vasoconstrictor is essential for hemostasis together with endoscopic variceal ligation (EVL). Standard-dose repeated bolus injection (SDRBI) of terlipressin 4–6 times daily is most widely employed before and after EVL, but the adverse effects of terlipressin cannot be overlooked. To minimize the ischemic side effect, low-dose continuous infusion (LDCI) of terlipressin has been proposed for hepato-renal syndrome in patients with liver cirrhosis. However, data from prospective comparisons between the two methods for AVB are sparse. This study aims to compare the safety and efficacy of the two methods for the management of AVB. Method: This study is a randomized controlled trial to compare SDRBI and LDCI of terlipressin in patients with AVB. A total of 125 patients were enrolled and randomly assigned to the SDRBI group (n = 63, 1 mg bolus injection every 6 hours after initial 2 mg of terlipressin) or LDCI group (n = 62, 2 mg/day of terlipressin infusion) after EVL. Patients with gastric varices on the fundus, failure of initial endoscopic therapy, or advanced hepatocellular carcinoma were excluded. Results: The baseline characteristics of the patients were not significantly different. Re-bleeding incidence after initial successful EVL was observed for 5 days. The success rate of maintaining hemostasis was 98.4% in both groups (Crude odd ratio = 0.98 [0.06– 6.09], P = 0.991). One patient died in the SDRBI group. Decrease of Hb more than 3 g/dL or adjusted blood requirement index over 0.75 to maintain Hb>8.0 g/dL were observed in 7 patients (11.1%) in the SDRBI and 9 (14.5%) in the LDCI group (P = 0.763), respectively, without newly developed hematemesis or melena. The overall incidence of gastrointestinal, cardiovascular, metabolic, or neurologic adverse events was significantly higher in the SDRBI group than in the LDCI group during 5 days (P < 0.05). Conclusion: Compared with SDRBI, LDCI of terlipressin shows comparable efficacy and better safety for managing AVB in patients with liver cirrhosis.